Medical Methods for First-Trimester Abortion

Clinical Scenario

A 34-year-old patient, gravida 3, para 2, has an unplanned pregnancy and requests referral for abortion. Her last menstrual period began 39 days ago. She asks what you know about “the abortion pill.”

Cochrane Abstract

Background. Surgical abortion by vacuum aspiration or dilatation and curettage up to 63 days’ gestation has been the method of choice since the 1960s. Medical abortion became an alternative method of first-trimester pregnancy termination with the availability of prostaglandins in the early 1970s and anti-progesterones in the 1980s. The most widely researched drugs are prostaglandins alone, mifepristone alone, methotrexate alone, mifepristone with prostaglandins, and methotrexate with prostaglandins.

Objectives. To compare different medical methods for first-trimester abortion.

Search Strategy. The authors1 searched the Cochrane Controlled Trials Register, MEDLINE, and Popline. Reference lists of retrieved papers also were searched. Experts in the World Health Organization Human Reproduction Programme were contacted.

Selection Criteria. Randomized controlled trials comparing different methods (e.g., single-drug and combination regimens), methods of application, or dosage regimens for medical abortion were considered. After assessment, trials were included if they had adequate randomization procedure, concealment of allocation, and follow-up. Women in the first trimester of pregnancy who were undergoing medical abortion were the participants. Different medical methods used for first-trimester abortion, compared with each other or placebo, were included. Outcomes included mortality, failure to achieve complete abortion, surgical evacuation (as emergency procedure, non-emergency procedure, or undefined), ongoing pregnancy at follow-up, time until passing of conceptus (more than three to six hours), blood transfusion, blood loss (measured or clinically relevant drop in hemoglobin), days of bleeding, pain resulting from the procedure (reported by the women or measured by use of analgesics), additional uterotonics used, women’s dissatisfaction with the procedure, nausea, vomiting, and diarrhea.

Data Collection and Analysis. Two reviewers independently selected trials for inclusion from the results of the search strategy described previously. Trials under consideration were evaluated for appropriateness for inclusion and methodologic quality without consideration of their results. A form was designed to facilitate the data extraction. Data were processed using Revman software.

Primary Results. Thirty-nine trials were included in the review. Unless otherwise stated, the effectiveness outcomes refer to failure to achieve complete abortion with the intended method.

Mifepristone in a dosage of 600 mg compared with a dosage of 200 mg has similar effectiveness in achieving complete abortion (four trials; relative risk [RR], 1.07; 95 percent confidence interval [CI], 0.87 to 1.32). Misoprostol administered orally is less effective (more failures) than misoprostol administered vaginally (RR, 3.00; 95 percent CI, 1.44 to 6.24) and may be associated with more frequent side effects, such as nausea and diarrhea.

Mifepristone alone is less effective than a combination of mifepristone and prostaglandin (RR, 3.76; 95 percent CI, 2.30 to 6.15). Similarly, all but one of the five trials comparing prostaglandin with the combined regimen reported higher effectiveness with the combined regimen. The results of these studies were not pooled, but the RR of failure with prosta-glandin alone is between 1.4 and 3.75, and the 95 percent CI indicates statistical significance.

In one trial comparing gemeprost in a dosage of 0.5 mg with misoprostol in a dosage of 800 mcg, misoprostol was more effective (failure with gemeprost: RR, 2.86; 95 percent CI, 1.14 to 7.18). [Editor’s note: Gemeprost is a prostaglandin available in the United Kingdom but not in the United States.] There was no difference between using a split dose or a single dose of prostaglandin.

There was no statistically significant difference in failure to achieve complete abortion when intramuscular methotrexate was compared with oral methotrexate (RR, 2.04; 95 percent CI, 0.51 to 8.07). Similarly, early (day 3) versus late (day 5) administration of prostaglandin showed no significant difference (RR, 0.72; 95 percent CI, 0.36 to 1.43). One trial compared the effects of tamoxifen versus methotrexate, and no statistically significant differences were observed between the groups.

Reviewers’ Conclusions. Safe and effective medical abortion methods are available. Combined regimens are more effective than use of single agents. In the combined regimen, the dosage of mifepristone can be lowered to 200 mg without significantly decreasing effectiveness. Vaginal misoprostol is more effective than oral misoprostol. Some results are based on small studies only and therefore carry some uncertainty. Almost all trials were conducted in hospital settings with good access to support and emergency services. It is therefore not clear if the results are readily applicable to under-resourced settings where such services are lacking, even if the agents used are available.

These summaries have been derived from Cochrane reviews published in the Cochrane Database of Systematic Reviews in The Cochrane Library. Their content has, as far as possible, been checked with the authors of the original reviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minor editing changes have been made to the text (www.cochrane.org).

Clinical Question

What are the most effective regimens for first-trimester medical abortion?

Evidence-Based Answer

A regimen that includes mifepristone in a dosage of 200 mg administered orally, followed by misoprostol in a dosage of 800 mcg administered vaginally, is highly effective for medical abortion up to 63 days’ gestation. Side effects include bleeding, pain, nausea, vomiting, and diarrhea. Serious complications are rare. In settings where mifepristone is unavailable, methotrexate, followed by misoprostol, is effective up to 49 days’ gestation.

Practice Pointers

In the United States, 49 percent of all pregnancies are unintended, and about one half of women with an unintended pregnancy choose abortion.2 The U.S. Food and Drug Administration (FDA) has approved mifepristone (also known as RU-486) for use with the prostaglandin misoprostol to induce medical abortion up to 49 days after the last menstrual period.

The original FDA-approved protocol is based on early clinical trials in the United States and France. On the first visit, after appropriate counseling and dating ultrasonography, the patient takes 600 mg of mifepristone orally. She returns on day 3 to take 400 mcg of misoprostol orally, and again on day 14 for a follow-up examination and ultrasonography to ensure that the abortion is complete.

Based on evidence from recent trials, including those in the Cochrane Review, current practice patterns include several variations of this protocol, incorporating the following changes: using a lower dosage (200 mg) of oral mifepristone; administering 800 mcg of misoprostol vaginally instead of orally; allowing the patient to use misoprostol at home on day 2, 3, or 4; and following up sooner than 14 days. This protocol is used until 63 days’ gestation. These variations are equally effective and allow more flexibility for patients. Vaginal misoprostol causes fewer gastrointestinal side effects than oral misoprostol.

The rate of complete abortion with mifepristone and misoprostol was 92 to 95 percent using the FDA-approved regimen.3,4 Data in this review were insufficient to describe differences in efficacy by gestational age, but a recent study using the evidence-based regimen reported completion rates of 96 to 97 percent, including pregnancies up to 63 days’ gestation.5 Patients choosing medical abortion must consent to undergo vacuum aspiration in cases of incomplete abortion. Misoprostol and methotrexate can cause fetal anomalies.

Prior to mifepristone’s approval in the United States, medical abortion regimens were developed that used methotrexate in combination with prostaglandins. None of the reviewed studies compared methotrexate with mifepristone. One high-quality, unblinded, randomized controlled trial comparing methotrexate (50 mg per m2 intramuscularly) with mifepristone (200 mg orally), each followed by 800 mcg of vaginal misoprostol, reported similar success rates, side effects, and complications up to 49 days’ gestation.6 Time to completion of the abortion was shorter with the mifepristone-based regimen.

Common side effects of medical abortion include pain and bleeding from the abortion itself; these effects may be comparable to those of an early miscarriage, except that the timing of bleeding is more predictable. Other side effects of prostaglandin use may include nausea, vomiting, diarrhea, low-grade fever, and chills. Most side effects can be managed with oral analgesics and careful counseling. Complications of medical abortion, such as hemorrhage and infection, are rare. Bleeding that requires transfusion occurs in approximately 0.2 percent of cases.1 Infection is less frequent.7 The current review did not address differences in side effects, bleeding patterns, and acceptability of the various regimens.

Almost all of the studies in the current review were conducted in hospital-based clinics with access to ultrasonography and surgical abortion services. Caution should be used when applying this research to settings with fewer resources. In summary, medical abortion is a safe, effective, noninvasive alternative to early surgical abortion.

The Authors

MELISSA NOTHNAGLE, M.D., is clinical assistant professor of family medicine and assistant residency director in family medicine at Brown Medical School in Providence, R.I....

JULIE SCOTT TAYLOR, M.D., M.SC., is assistant professor of family medicine and director of predoctoral education in family medicine at Brown Medical School.

Address correspondence to Melissa Nothnagle, M.D., Department of Family Medicine, Memorial Hospital of Rhode Island, 111 Brewster St., Providence, RI 02860 (e-mail: Melissa_nothnagle@mhri.org). Reprints are not available from the authors.

The information and opinions presented in AFP reflect the views of the authors, not those of the journal or the American Academy of Family Physicians, unless so stated. The Academy’s policy on reproductive decisions, including medical abortion, is available online at: https://www.aafp.org/x7053.xml.

The Cochrane Abstract is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. Melissa Nothnagle, M.D., and Julie Scott Taylor, M.D., M.Sc., present a clinical scenario and question based on the Cochrane Abstract, along with the evidence-based answer and a full critique of the abstract.